Future Research Directions with TcArsl: Addressing the Hazards Associated with Arsenic Pollution
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Arsenic is a potent carcinogenic environmental toxin that is generated from natural and anthropogenic activities. Microorganisms play an active role in the biotransformation of arsenic. Microorganisms contain non-heme ferrous-dependent dioxygenase enzyme (Arsl) which converts toxic methylarsenite (III) into inorganic arsenite. An Arsl ortholog, TcArsl , have been recently isolated from the thermophilic bacteria Thermonospora curvata. The enzyme binds with methylarsenite by a pair of cysteine residues in its active site. The structure-function relationships of the enzyme were elucidated after appropriate purification and crystallization. The structure –function relationships indicated a loop-gating mechanism for controlling the catalytic reactions. TcArsl acts by cleaving the C-As bond of methylarsenite. The structure of the enzyme was resolved in both apo form and by using Ni(II), Co(II) or Fe(II) as prosthetic groups.
Future studies should be conducted to elucidate the enzymatic mechanism of TcArsl. Research areas should focus on identifying the impact of single nucleotide polymorphisms (specifically at the active site of the enzyme) on methylarsenite metabolism. Moreover, future studies should also explore the role of allosteric modulators (if any) in influencing the kinetics of TcArsl. Studies should also be carried out for identifying the competitive, noncompetitive and uncompetitive inhibitors of the respective enzyme.
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Michelis and Hill kinetics (with or without competitors/modulators) should also be elucidated for the respective enzyme. Such analysis would help to identify the turnover number or kcat values of the enzyme under specific conditions. Research should also be carried to explore the impact of the change in pH on enzyme kinetics. Such information could be used for forecasting the biodegradation organochlorine pesticides. The future research directions would greatly aid in addressing the hazards associated with arsenic pollution.
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